Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) infection, being one of the most prevalent diseases in the world. In human tuberculosis, the most common one is pulmonary tuberculosis, accounting for 80-90% of the total number of organ tuberculosis. Due to the emergence of drug-resistant tuberculosis and AIDS co-infection, the existing clinical drug treatment effect is greatly reduced.
According to the 18th WHO Global Tuberculosis Report, there are about 8.6 million new tuberculosis patients worldwide in 2012, with a death toll of 1.3 million. In China, the incidence of tuberculosis accounts for 12% of the world's incidence (1 million people) ranking second in the world, and the death toll of 44,000 ranking fifth in the world. Multi-drug resistant tuberculosis further widely spreads in this world, and there are about 450,000 new cases of resistance in 2012. And China is one of the 27 countries with severe multi-drug resistant tuberculosis epidemic in the world, and about 1.6 million people are reported as multi-drug resistant tuberculosis.
The current treatment is a combination therapy of the first-line drugs isoniazid, rifampicin, pyrazinamide and ethambutol etc. with the second-line drugs, with a treatment time of 6-9 months, which does not have good treatment effect on drug resistant mycobacterium tuberculosis and persister bacteria and brings great distress and economic bureden to patients. Resistance mechanisms of first-line anti-TB drugs currently used have been relatively clear, that is mainly due to improper use of drugs, mutation of the corresponding target gene or drug activation related enzyme gene or related regulatory gene occur, resulting in drug failure. As a result, at the launch of the Global Alliance for TB Drug Development, people have begun to re-focus on the development of anti-TB drugs. The new drug should have the following characteristics: (1) developing a new drug that can shorten the treatment cycle; (2) developing a drug that is effective against drug-resistant mycobacterium tuberculosis; (3) developing a new drug that can effectively treat latent bacterial infections.
There are three main aspects of research and development of anti-tuberculosis drugs: natural selection, design and synthesis of a new structure type compound, and re-modification of an antibacterial drug. In recent years, some new synthetic anti-TB drugs at home and abroad are quinoline, nitroimidazopyrans, oxazolidinones, pyrrole, imidazopyridines and so on. At the end of 2012, the bis-arylquinoline drug bedaquiline was accelerated approved by the FDA for approval as one of the components of the adult MDR-TB treatment program, and this is the first new anti-tuberculosis drug since the introduction of rifampicin in 1970. But the follow-up clinical trials show that bedaquiline also showed a certain side effects, and security risks still exist. Therefore, it is of great significance to further develop a safe and effective anti-tuberculosis drug to overcome the risk of clinically drug-resistant tuberculosis.